Core target gene screening and mechanism analysis of Tongfu Xiefei formula in treatment of ARDS

YUAN Xinye; LU Jun

doi:10.3969/j.issn.1002-266X.2025.03.002

Abstract：Objective To identify the core target genes of Tongfu Xiefei formula in the treatment of acute respiratory distress syndrome(ARDS)using network pharmacology and to explore its potential mechanism of action.Methods The active ingredients of Tongfu Xiefei formula were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Simplified molecular input-line entry system(SMILES)data for these ingredi-ents were obtained from databases such as PubChem.Target genes of the active ingredients were retrieved from the TCMSP database and were further screened using the SwissTargetPrediction platform.ARDS-related disease target genes were col-lected from the DisGeNet,GeneCards,and OMIM disease databases.The intersection of target genes from Tongfu Xiefei formula's active ingredients and ARDS-related genes was analyzed to select potential therapeutic target genes.These target genes were imported into the STRING 12.0 database to construct a protein-protein interaction(PPI)network,from which core target genes for ARDS treatment with Tongfu Xiefei formula were identified.Data for the active ingredients and poten-tial therapeutic target genes were input into the Cytoscape 3.10.2 software.The"Analyze Network"function was used to study the network.The top six active ingredients with the highest Degree values were selected as the core ingredients of the formula.Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted on the core target genes,and molecular docking was used to assess the binding affinity between the core active ingredients and target genes.Results A total of 78 active ingredients of Tongfu Xiefei formula were iden-tified,corresponding to 729 target genes.A total of 3,207 ARDS-related target genes were retrieved.The intersection analysis revealed 322 target genes,which were considered as potential therapeutic targets for ARDS treatment;59 core tar-get genes were identified,including IL-6,AKT1,and tumor necrosis factor(TNF),etc.The core active ingredients of the formula identified for ARDS treatment were quercetin,kaempferol,luteolin,3',4',5,7-tetramethoxyflavone,isorhamne-tin,and 4',5,7-trimethoxyflavone.GO and KEGG pathway enrichment analyses indicated that the core target genes played a significant role in regulating signal transduction,enzyme activity,and energy transfer.These genes mainly affect-ed pathways such as the PD-L1/PD-1 checkpoint pathway,HIF-1 signaling pathway,Ras signaling pathway,and PI3K-Akt signaling pathway,etc.Molecular docking results demonstrated that the core active ingredients exhibited strong bind-ing affinities with their corresponding target proteins.Conclusions The core target genes of Tongfu Xiefei formula for treatment of ARDS include IL-6,AKT1,and TNF,etc.The mechanism of action is related to the regulation of the PD-L1/PD-1 checkpoint pathway,HIF-1 signaling pathway,Ras signaling pathway,PI3K-Akt signaling pathway,and other relat-ed pathways.